Analysing the human-coronavirus RNA interactome.
RNA is the direct product of the genes of all living organisms. The infectious ingredient of most human viruses, including coronaviruses, is RNA. RNA viruses are often considered to present the highest threat for triggering pandemics, as illustrated by SARS-CoV-2, the causative agent of COVID-19. The infection cycle of SARS-CoV-2 takes place mainly in the cytoplasm of the host cell, where many cellular RNAs reside. Virus and host RNA molecules can interact with each other by 'base-pairing' along parts of their structure. Such interactions may offer unique targets for anti-viral therapies, and indeed an anti-hepatitis C virus drug targeting such interaction is currently in clinical trials. However, the prevalence of naturally occurring host-virus RNA-RNA interactions is unknown, and discoveries of new interactions are rare.
Omer Ziv and his colleagues are now employing cutting-edge tools to dissect the crosstalk between the human and the coronavirus RNA. They have recently developed a new technique, named COMRADES, that provides an opportunity to dissect the host-virus RNA interactome. Such interactions are frequently unstable and are therefore easily disrupted when RNA is collected and analysed. The COMRADES method overcomes this obstacle by utilising small molecules to 'glue' RNA base-pairing inside cells. Applying COMRADES to SARS-CoV-2 and to a related coronavirus (MERS-CoV) provides a snapshot of all RNA structures and interactions as they occur during coronavirus infection. The team are employing the resulting data for an educated design of molecules capable of interfering with host-virus RNA base-pairing and are testing their potential to slow down COVID-19. This research provides a unique opportunity to identify new RNA-based viral pathways and has the potential to open up new therapeutic opportunities.
Publications
Ziv O, Price J, Shalamova L, Kamenova T, Goodfellow I, Weber F, Miska E (2020). The short- and long-range RNA-RNA interactome of SARS-CoV-2. Mol. Cell, Advance online publication. doi: 10.1016/j.molcel.2020.11.004